TY - JOUR
T1 - Oxidative damage to nucleic acids in severe emphysema
AU - Deslee, Gaetan
AU - Woods, Jason C.
AU - Moore, Carla
AU - Conradi, Susan H.
AU - Gierada, David S.
AU - Atkinson, Jeffrey J.
AU - Battaile, John T.
AU - Liu, Lucy
AU - Alexander Patterson, G.
AU - Adair-Kirk, Tracy L.
AU - Holtzman, Michael J.
AU - Pierce, Richard A.
N1 - Funding Information:
This study was supported by National Institutes of Health grant P50HL084922. Dr. Deslee received grants for postdoctoral training from Region Champagne-Ardenne, University and CHU of Reims, ARAIRCHAR, College des Professeurs de Pneumologie and AstraZeneca.
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Background: Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Methods: Thirteen human severe emphysematous lungs, including five with α1-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Results: Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. Conclusions: We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.
AB - Background: Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Methods: Thirteen human severe emphysematous lungs, including five with α1-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Results: Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. Conclusions: We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.
KW - Emphysema
KW - Nucleic acids
KW - Oxidative stress
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=64749097430&partnerID=8YFLogxK
U2 - 10.1378/chest.08-2257
DO - 10.1378/chest.08-2257
M3 - Article
C2 - 19118262
AN - SCOPUS:64749097430
SN - 0012-3692
VL - 135
SP - 965
EP - 974
JO - CHEST
JF - CHEST
IS - 4
ER -